Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives

Das, Arnika; Greco, Giulia; Kumar, Sujeet; Catanzaro, Elena; Morigi, Rita; Locatelli, Alessandra; Schols, Dominique; Alıcı, Hakan; Tahtacı, Hakan; Ravindran, Febina; Fimognari, Carmela; Karki, Subhas S.

doi:10.1016/j.compbiolchem.2022.107641

Cited by 4 publications

(1 citation statement)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the pyrazole and indolin‐2‐one based compounds have presented extensive biological properties, such as antitumoral, [7,8,9,10] anti‐inflammatory, [11] and antimicrobial activities [11,12,13] . Similarly the 2‐oxindole derivatives have been previously described as cytotoxic, [14,15] antimicrobial, [16] antiviral, [17] Ligase‐1 [18] and BCL 2 inhibitors, [19,20] and as anticancer agents [21,22] (Figure 1). The objective of the present investigation was to synthesize and characterize pyrazoles with 2‐oxindole conjugates ( 6a – 6k ) as anti‐cancer agents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pyrazole‐Oxindole Conjugates with Cytotoxicity in Human Cancer Cells via Apoptosis

Karki

Jain

Gutierrez

et al. 2023

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

A novel series of pyrazole‐oxindole conjugates were prepared and characterized as potential cytotoxic agents by FT‐IR, NMR and HR‐MS. The cytotoxic activity of these compounds was tested in the Jurkat acute T cell leukemia, CEM acute lymphoblastic leukemia, MCF10 A mammary epithelial and MDA‐MB 231 triple negative breast cancer cell lines. Among the tested conjugates, 5‐methyl‐3‐((3‐(1‐phenyl)‐3‐(p‐tolyl)‐1H‐pyrazol‐4‐yl)methylene)indolin‐2‐one 6h emerged as the most cytotoxic with a CC50 of 4.36+/−0.2 μM against Jurkat cells. The mechanism of cell death induced by 6h was investigated through the Annexin V‐FITC assay via flow cytometry. Reactive oxygen species (ROS) accumulation, mitochondrial health and the cell cycle progression were also evaluated in cells exposed to 6h. Results demonstrated that 6h induces apoptosis in a dose‐response manner, without generating ROS and/or altering mitochondrial health. In addition, 6h disrupted the cell cycle distribution causing an increase in DNA fragmentation (Sub G0‐G1), and an arrest in the G0‐G1 phase. Taken together, the 6h compound revealed a strong potential as an antineoplastic agent evidenced by its cytotoxicity in leukemia cells, the activation of apoptosis and restriction of the cell cycle progression.

show abstract